Nasopharyngeal Carriage of S. Pneumoniae

NCT04460313 | Recruiting DMC

• 1 other identifier: ACT0806
• Study Type: interventional
• Target: 25,760
• Locations: 1 country
• Sites: 1

Brief Summary

This nasopharyngeal (NP) carriage surveillance study was requested by the European Agency for the Evaluation of Medicinal Products as a post-licensing commitment to determine whether the use of the pneumococcal conjugate vaccines (PCVs) including 7 then 13 valents (introduced in 2001 and 2010, respectively) caused a shift in the distribution of Streptococcus pneumoniae serotypes in children with acute otitis media and modified the resistance of this bacterial species to antibiotics.

Conditions

Nasopharyngeal Carriage; Children, Only; Antibiotic Resistant Strain

Keywords

Pneumococcal conjugate vaccine; Streptococcus pneumoniae; Carriage

Outcome Measures

Primary Outcomes (6)

• S. Pneumoniae colonisation

  Percentage of children colonised by S. Pneumoniae

  at inclusion

• S. Pneumoniae colonisation involving to vaccine serotypes

  Percentage of children colonised by vaccine serotypes

  at inclusion

• S. Pneumoniae colonisation involving to non vaccine serotypes

  Percentage of children colonised by non vaccine serotypes

  at inclusion

• Reduced of sensitivity to penicillin

  Percentage of Sp carriers with reduced sensitivity to penicillin

  at inclusion

• Detect the emergence of new serotypes

  Percentage of emerging serotypes detected (\> 10 Percent of isolated Sp, 5 percent of carrier children)

  at inclusion

• Association of Pneumococcal Serotypes with Respiratory Viruses

  Percentage of pneumococcal serotypes associated with various respiratory viruses (SARS-CoV-2, RSV, Influenza A, Influenza B) in children with AOM.

  at inclusion

Secondary Outcomes (3)

• Detect the emergence of resistance S. pneumoniae

  at inclusion

• Evaluation of nasopharyngeal carriage of other bacteria

  at inclusion

• For the ancillary study, the resistance of E. coli (ESBL) will be evaluated.

  at inclusion

Study Arms (3)

prospective cohort: Main study

OTHER

700 children aged 6 to 36 months with AOM and 500 healthy control children aged 6 months to 15 years will be enrolled. A mandatory nasopharyngeal swab is planned for these groups.

Other: nasopharyngeal sample (mandatory)

ESBL cohort- Ancillary study

OTHER

For a subgroup of approximately 500 children with AOM, aged 6 to 24 months, optional stool or anorectal swab samples will be collected.

Other: nasopharyngeal sample (mandatory); Other: Stools collection or anorectal swab samples (optional); Other: nasopharyngeal sample (optional)

Optional Nasopharyngeal sample

OTHER

For a subgroup of 560 children with AOM, an optional nasal sample will be collected to assess the association of various respiratory viruses (SARS-CoV-2, RSV, Influenza A, Influenza B) with different pneumococcal serotypes.

Other: nasopharyngeal sample (mandatory); Other: nasopharyngeal sample (optional)

Interventions

nasopharyngeal sample (mandatory) OTHER

A mandatory nasopharyngeal swab is planned for each included patient: patients aged 6 to 36 months with AOM and control children (healthy) aged 6 months to 15 years. The bacteriological analyses will be carried out by the French National Reference Centre for Pneumococci.

ESBL cohort- Ancillary study; Optional Nasopharyngeal sample; prospective cohort: Main study

Stools collection or anorectal swab samples (optional) OTHER

For a subgroup of AOM children aged 6 to 36 months, stools samples or anorectal swab samples were collected for assessment of E. coli (ESBL) resistance

ESBL cohort- Ancillary study

nasopharyngeal sample (optional) OTHER

Optional nasopharyngeal swabs from children with AOM aged 6 to 36 months to assess the association of various respiratory viruses (SARS-CoV-2, RSV, Influenza A, Influenza B) with different pneumococcal serotypes.

ESBL cohort- Ancillary study; Optional Nasopharyngeal sample

Eligibility Criteria

• Age: 6 Months - 15 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• both sexes
• suffering from suppurative AOM or healthy children
• age: 6 months to 36 months for AOM
• age: 6 months to 15 years for healthy children
• informed consent from parents or guardians
• Children who haven't received antibiotic treatment within 7 days before enrollment,

You may not qualify if:

• severe underlying disease,
• Children with bullous myringitis cannot be included.

Sponsors & Collaborators

• Association Clinique Thérapeutique Infantile du val de Marne: lead
• Pfizer: collaborator

Study Sites (1)

ACTIV

Créteil, France

RECRUITING

Related Publications (20)

• Levy C, Varon E, Bechet S, Bonacorsi S, Cohen R. Similarities and Differences Between Countries When Estimating the Effect of Higher-valency Pneumococcal Conjugate Vaccines on Colonization and Acute Otitis Media. Pediatr Infect Dis J. 2025 May 1;44(5):e184-e186. doi: 10.1097/INF.0000000000004686. Epub 2025 Jan 21. No abstract available.

  PMID: 39841925 BACKGROUND

• Ouldali N, Cohen R, Levy C, Gelbert-Baudino N, Seror E, Corrard F, Vie Le Sage F, Michot AS, Romain O, Bechet S, Bonacorsi S, Angoulvant F, Varon E. Pneumococcal susceptibility to antibiotics in carriage: a 17 year time series analysis of the adaptive evolution of non-vaccine emerging serotypes to a new selective pressure environment. J Antimicrob Chemother. 2019 Oct 1;74(10):3077-3086. doi: 10.1093/jac/dkz281.

  PMID: 31280295 RESULT

• Rybak A, Levy C, Bonacorsi S, Bechet S, Vie le Sage F, Elbez A, Varon E, Cohen R. Antibiotic Resistance of Potential Otopathogens Isolated From Nasopharyngeal Flora of Children With Acute Otitis Media Before, During and After Pneumococcal Conjugate Vaccines Implementation. Pediatr Infect Dis J. 2018 Mar;37(3):e72-e78. doi: 10.1097/INF.0000000000001862.

  PMID: 29227464 RESULT

• Birgy A, Bidet P, Levy C, Sobral E, Cohen R, Bonacorsi S. CTX-M-27-Producing Escherichia coli of Sequence Type 131 and Clade C1-M27, France. Emerg Infect Dis. 2017 May;23(5):885. doi: 10.3201/eid2305.161865. No abstract available.

  PMID: 28418829 RESULT

• Cohen R, Varon E, Doit C, Schlemmer C, Romain O, Thollot F, Bechet S, Bonacorsi S, Levy C. A 13-year survey of pneumococcal nasopharyngeal carriage in children with acute otitis media following PCV7 and PCV13 implementation. Vaccine. 2015 Sep 22;33(39):5118-26. doi: 10.1016/j.vaccine.2015.08.010. Epub 2015 Aug 11.

  PMID: 26271823 RESULT

• Cohen R, Levy C, Bonnet E, Thollot F, Boucherat M, Fritzell B, Derkx V, Bingen E, Varon E. Risk factors for serotype 19A carriage after introduction of 7-valent pneumococcal vaccination. BMC Infect Dis. 2011 Apr 18;11:95. doi: 10.1186/1471-2334-11-95.

  PMID: 21501471 RESULT

• Cohen R, Bingen E, Levy C, Thollot F, Boucherat M, Derkx V, Varon E. Nasopharyngeal flora in children with acute otitis media before and after implementation of 7 valent pneumococcal conjugate vaccine in France. BMC Infect Dis. 2012 Mar 7;12:52. doi: 10.1186/1471-2334-12-52.

  PMID: 22397629 RESULT

• Levy C, Vie le Sage F, Varon E, Chalumeau M, Grimprel E, Cohen R. Pediatric Ambulatory and Hospital Networks for Surveillance and Clinical Epidemiology of Community-Acquired Infections. J Pediatr. 2018 Mar;194:269-270.e2. doi: 10.1016/j.jpeds.2017.11.050. Epub 2018 Feb 22. No abstract available.

  PMID: 29637893 RESULT

• Vermee Q, Cohen R, Hays C, Varon E, Bonacorsi S, Bechet S, Thollot F, Corrard F, Poyart C, Levy C, Raymond J. Biofilm production by Haemophilus influenzae and Streptococcus pneumoniae isolated from the nasopharynx of children with acute otitis media. BMC Infect Dis. 2019 Jan 11;19(1):44. doi: 10.1186/s12879-018-3657-9.

  PMID: 30634919 RESULT

• Birgy A, Madhi F, Jung C, Levy C, Cointe A, Bidet P, Hobson CA, Bechet S, Sobral E, Vuthien H, Ferroni A, Aberrane S, Cuzon G, Beraud L, Gajdos V, Launay E, Pinquier D, Haas H, Desmarest M, Dommergues MA, Cohen R, Bonacorsi S; Group of the National Observatory of Urinary tract Infection due to ESBL-producing Enterobacteriaceae in children. Diversity and trends in population structure of ESBL-producing Enterobacteriaceae in febrile urinary tract infections in children in France from 2014 to 2017. J Antimicrob Chemother. 2020 Jan 1;75(1):96-105. doi: 10.1093/jac/dkz423.

  PMID: 31617912 RESULT

• Mizrahi A, Cohen R, Varon E, Bonacorsi S, Bechet S, Poyart C, Levy C, Raymond J. Non typable-Haemophilus influenzae biofilm formation and acute otitis media. BMC Infect Dis. 2014 Jul 19;14:400. doi: 10.1186/1471-2334-14-400.

  PMID: 25037572 RESULT

• Birgy A, Levy C, Bidet P, Thollot F, Derkx V, Bechet S, Mariani-Kurkdjian P, Cohen R, Bonacorsi S. ESBL-producing Escherichia coli ST131 versus non-ST131: evolution and risk factors of carriage among French children in the community between 2010 and 2015. J Antimicrob Chemother. 2016 Oct;71(10):2949-56. doi: 10.1093/jac/dkw219. Epub 2016 Jun 20.

  PMID: 27330068 RESULT

• Hau I, Levy C, Caeymaex L, Cohen R. Impact of pneumococcal conjugate vaccines on microbial epidemiology and clinical outcomes of acute otitis media. Paediatr Drugs. 2014 Feb;16(1):1-12. doi: 10.1007/s40272-013-0044-2.

  PMID: 23963858 RESULT

• Birgy A, Cohen R, Levy C, Bidet P, Courroux C, Benani M, Thollot F, Bingen E. Community faecal carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae in French children. BMC Infect Dis. 2012 Nov 21;12:315. doi: 10.1186/1471-2334-12-315.

  PMID: 23171127 RESULT

• Caeymaex L, Varon E, Levy C, Bechet S, Derkx V, Desvignes V, Doit C, Cohen R. Characteristics and outcomes of acute otitis media in children carrying streptococcus pneumoniae or haemophilus influenzae in their nasopharynx as a single otopathogen after introduction of the heptavalent pneumococcal conjugate vaccine. Pediatr Infect Dis J. 2014 May;33(5):533-6. doi: 10.1097/INF.0000000000000213.

  PMID: 24263220 RESULT

• Cohen R, Levy C, Bingen E, Koskas M, Nave I, Varon E. Impact of 13-valent pneumococcal conjugate vaccine on pneumococcal nasopharyngeal carriage in children with acute otitis media. Pediatr Infect Dis J. 2012 Mar;31(3):297-301. doi: 10.1097/INF.0b013e318247ef84.

  PMID: 22330166 RESULT

• Cohen R, Levy C, Bingen E, Bechet S, Derkx V, Werner A, Koskas M, Varon E. [Nasopharyngeal carriage of children 6 to 60 months during the implementation of the 13-valent pneumococcal conjugate vaccine]. Arch Pediatr. 2012 Oct;19(10):1132-9. doi: 10.1016/j.arcped.2012.07.013. Epub 2012 Aug 24. French.

  PMID: 22925540 RESULT

• Cohen R, Levy C, Thollot F, de La Rocque F, Koskas M, Bonnet E, Fritzell B, Varon E. Pneumococcal conjugate vaccine does not influence Staphylococcus aureus carriage in young children with acute otitis media. Clin Infect Dis. 2007 Dec 15;45(12):1583-7. doi: 10.1086/523734.

  PMID: 18190319 RESULT

• Cohen R, Levy C, de La Rocque F, Gelbert N, Wollner A, Fritzell B, Bonnet E, Tetelboum R, Varon E. Impact of pneumococcal conjugate vaccine and of reduction of antibiotic use on nasopharyngeal carriage of nonsusceptible pneumococci in children with acute otitis media. Pediatr Infect Dis J. 2006 Nov;25(11):1001-7. doi: 10.1097/01.inf.0000243163.85163.a8.

  PMID: 17072121 RESULT

• Assad Z, Cohen R, Varon E, Levy C, Bechet S, Corrard F, Werner A, Ouldali N, Bonacorsi S, Rybak A. Antibiotic Resistance of Haemophilus influenzae in Nasopharyngeal Carriage of Children with Acute Otitis Media and in Middle Ear Fluid from Otorrhea. Antibiotics (Basel). 2023 Nov 8;12(11):1605. doi: 10.3390/antibiotics12111605.

  PMID: 37998807 RESULT

Related Links

• ACTIV publications
• Similarities and Differences Between Countries When Estimating the Effect of Higher-valency Pneumococcal Conjugate Vaccines on Colonization and Acute Otitis Media

Study Officials

• Robert Cohen, MD

  Association Clinique Thérapeutique Infantile du val de Marne

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Corinne Levy, MD

CONTACT

0033148850404; corinne.levy@activ-france.fr

Stéphane Béchet, MsC

CONTACT

0033148850404; stephane.bechet@activ-france.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: multicenter nationwide prospective cohort

Study Record Dates

• First Submitted: June 19, 2020
• First Posted: July 7, 2020
• Study Start: September 11, 2001
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)